title: Kidney xenotransplantation.
abstract: Xenotransplantation using pigs as donors offers the possibility of eliminating the chronic shortage of donor kidneys, but there are several obstacles to be overcome before this goal can be achieved. Preclinical studies have shown that, while porcine renal xenografts are broadly compatible physiologically, they provoke a complex rejection process involving preformed and elicited antibodies, heightened innate immune cell reactivity, dysregulated coagulation, and a strong T cell-mediated adaptive response. Furthermore, the susceptibility of the xenograft to proinflammatory and procoagulant stimuli is probably increased by cross-species molecular defects in regulatory pathways. To balance these disadvantages, xenotransplantation has at its disposal a unique tool to address particular rejection mechanisms and incompatibilities: genetic modification of the donor. This review focuses on the pathophysiology of porcine renal xenograft rejection, and on the significant genetic, pharmacological, and technical progress that has been made to prolong xenograft survival.
authors.affiliation: 1] Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia [2] Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.affiliation: Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.affiliation: 1] Immunology Research Centre, St Vincent's Hospital, Melbourne, Victoria, Australia [2] Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Anthony J F
authors.initials: AJ
authors.lastname: d'Apice
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D030801:Animals, Genetically Modified; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects*; D010641:Phenotype; D013045:Species Specificity; D013552:Swine; D023001:Transplantation Tolerance; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents